Method of preparing naphthalocyanines

ABSTRACT

A method of preparing a naphthalocyanine is provided. The method comprises the steps of: (i) providing a tetrahydronaphthalic anhydride; (ii) converting said tetrahydronaphthalic anhydride to a benzisoindolenine; and (iii) macrocyclizing said benzisoindolenine to form a naphthalocyanine.

FIELD OF THE INVENTION

The present application relates generally to an improved method ofsynthesizing naphthalocyanines. It has been developed primarily toreduce the cost of existing naphthalocyanine syntheses and to facilitatelarge-scale preparations of these compounds.

CROSS REFERENCE TO OTHER RELATED APPLICATIONS

The following applications have been filed by the Applicantsimultaneously with this application:

-   -   Ser. Nos. 11/831,962 11/831,963

The disclosures of these co-pending applications are incorporated hereinby reference.

The following patents or patent applications filed by the applicant orassignee of the present invention are hereby incorporated bycross-reference.

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BACKGROUND OF THE INVENTION

We have described previously the use of naphthalocyanines asIR-absorbing dyes. Naphthalocyanines, and particularly galliumnaphthalocyanines, have low absorption in the visible range and intenseabsorption in the near-IR region (750-810 nm). Accordingly,naphthalocyanines are attractive compounds for use in invisible inks.The Applicant's U.S. Pat. Nos. 7,148,345 and 7,122,076 (the contents ofwhich are herein incorporated by reference) describe in detail the useof naphthalocyanine dyes in the formulation of inks suitable forprinting invisible (or barely visible) coded data onto a substrate.Detection of the coded data by an optical sensing device can be used toinvoke a response in a remote computer system. Hence, the substrate isinteractive by virtue of the coded data printed thereon.

The Applicant's netpage and Hyperlabel® systems, which makes use ofinteractive substrates printed with coded data, are describedextensively in the cross-referenced patents and patent applicationsabove (the contents of which are herein incorporated by reference).

In the anticipation of widespread adoption of netpage and Hyperlabel®technologies, there exists a considerable need to develop efficientsyntheses of dyes suitable for use in inks for printing coded data. Asforeshadowed above, naphthalocyanines and especially galliumnaphthalocyanines are excellent candidates for such dyes and, as aconsequence, there is a growing need to synthesize naphthalocyaninesefficiently and in high yield on a large scale.

Naphthalocyanines are challenging compounds to synthesize on a largescale. In U.S. Pat. Nos. 7,148,345 and 7,122,076, we described anefficient route to naphthalocyanines via macrocyclization ofnaphthalene-2,3-dicarbonitrile. Scheme 1 shows a route to the sulfonatedgallium naphthalocyanine 1 from naphthalene-2,3-dicarbonitrile 2, asdescribed in U.S. Pat. No. 7,148,345.

However, a problem with this route to naphthalocyanines is that thestarting material 2 is expensive. Furthermore,naphthalene-2,3-dicarbonitrile 2 is prepared from two expensive buildingblocks: tetrabromo-o-xylene 3 and fumaronitrile 4, neither of which canbe readily prepared in multi-kilogram quantities.

Accordingly, if naphthalocyanines are to be used in large-scaleapplications, there is a need to improve on existing syntheses.

SUMMARY OF THE INVENTION

In a first aspect, there is provided a method of preparing anaphthalocyanine comprising the steps of:

(i) providing a tetrahydronaphthalic anhydride;

(ii) converting said tetrahydronaphthalic anhydride to abenzisoindolenine; and

(iii) macrocyclizing said benzisoindolenine to form a naphthalocyanine.

Optionally, the tetrahydronaphthalic anhydride is of formula (I):

wherein:R₁, R₂, R₃ and R₄ are each independently selected from hydrogen,hydroxyl, C₁₋₂₀alkyl, C₁₋₂₀alkoxy, amino, C₁₋₂₀alkylamino,di(C₁₋₂₀alkyl)amino, halogen, cyano, thiol, C₁₋₂₀alkylthio, nitro, C₁₋₂₀alkylcarboxy, C₁₋₂₀alkylcarbonyl, C₁₋₂₀alkoxycarbonyl,C₁₋₂₀alkylcarbonyloxy, C₁₋₂₀alkylcarbonylamino, C₅₋₂₀aryl,C₅₋₂₀arylalkyl, C₅₋₂₀aryloxy, C₅₋₂₀arylalkoxy, C₅₋₂₀heteroaryl,C₅₋₂₀heteroaryloxy, C₅₋₂₀ heteroarylalkoxy or C₅₋₂₀heteroarylalkyl.

Optionally, R₁, R₂, R₃ and R₄ are all hydrogen.

Optionally, step (ii) comprises a one-pot conversion from thetetrahydronaphthalic anhydride to a benzisoindolenine salt. This one-potconversion facilitates synthesis of naphthalocyanines via the routedescribed above and greatly improves yields and scalability.

Optionally, the benzisoindolenine salt is a nitrate salt although othersalts (e.g., benzene sulfonate salt) are of course within the scope ofthe present invention.

Optionally, the one-pot conversion is effected by heating with a reagentmixture comprising ammonium nitrate.

Optionally, the reagent mixture comprises at least 2 equivalents ofammonium nitrate with respect to the tetrahydronaphthalic anhydride.

Optionally, the reagent mixture comprises urea.

Optionally, the reagent mixture comprises at least one further ammoniumsalt.

Optionally, the further ammonium salt is selected from: ammonium sulfateand ammonium benzenesulfonate.

Optionally, the reagent mixture comprises a catalytic amount of ammoniummolybdate.

Optionally, the heating is within a temperature range of 150 to 200° C.

The reaction may be performed in the presence of or in the absence of asolvent. Optionally, heating is in the presence of an aromatic solvent.Examples of suitable solvents are nitrobenzene, biphenyl, diphenylether, mesitylene, anisole, phenetole, dichlorobenzene, trichlorobenzeneand mixtures thereof.

Optionally, the benzisoindolenine is liberated from thebenzisoindolenine salt using a base. Sodium methoxide is an example of asuitable base although the skilled person will be readily aware of othersuitable bases.

Optionally, the benzisoindolenine is of formula (II):

wherein:R₁, R₂, R₃ and R₄ are each independently selected from hydrogen,hydroxyl, C₁₋₂₀alkyl, C₁₋₂₀alkoxy, amino, C₁₋₂₀alkylamino,di(C₁₋₂₀alkyl)amino, halogen, cyano, thiol, C₁₋₂₀alkylthio, nitro, C₁₋₂₀alkylcarboxy, C₁₋₂₀alkylcarbonyl, C₁₋₂₀alkoxycarbonyl,C₁₋₂₀alkylcarbonyloxy, C₁₋₂₀alkylcarbonylamino, C₅₋₂₀aryl,C₅₋₂₀arylalkyl, C₅₋₂₀aryloxy, C₅₋₂₀arylalkoxy, C₅₋₂₀heteroaryl,C₅₋₂₀heteroaryloxy, C₅₋₂₀ heteroarylalkoxy or C₅₋₂₀heteroarylalkyl.

Optionally, the naphthalocyanine is of formula (III):

wherein:R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅ and R₁₆are each independently selected from hydrogen, hydroxyl, C₁₋₂₀alkyl,C₁₋₂₀alkoxy, amino, C₁₋₂₀alkylamino, di(C₁₋₂₀alkyl)amino, halogen,cyano, thiol, C₁₋₂₀alkylthio, nitro, C₁₋₂₀alkylcarboxy,C₁₋₂₀alkylcarbonyl, C₁₋₂₀alkoxycarbonyl, C₁₋₂₀ alkylcarbonyloxy,C₁₋₂₀alkylcarbonylamino, C₅₋₂₀aryl, C₅₋₂₀arylalkyl, C₅₋₂₀aryloxy,C₅₋₂₀arylalkoxy, C₅₋₂₀ heteroaryl, C₅₋₂₀heteroaryloxy,C₅₋₂₀heteroarylalkoxy or C₅₋₂₀heteroarylalkyl;M is absent or selected from Si(A¹)(A²), Ge(A¹)(A²), GA(A¹), Mg, Al(A¹),TiO, Ti(A¹)(A²), ZrO, Zr(A¹)(A²), VO, V(A¹)(A²), Mn, Mn(A¹), Fe, Fe(A¹),Co, Ni, Cu, Zn, Sn, Sn(A¹)(A²), Pb, Pb(A¹)(A²), Pd and Pt;A¹ and A² are axial ligands, which may be the same or different, and areselected from —OH, halogen or —OR^(q);R^(q) is selected from C₁₋₁₆alkyl, C₅₋₂₀aryl, C₅₋₂₀arylalkyl,C₁₋₂₀alkylcarbonyl, C₁₋₂₀alkoxycarbonyl or Si(R^(x))(R^(y))(R^(z)); andR^(x), R^(y) and R^(z) may be the same or different and are selectedfrom C₁₋₂₀alkyl, C₅₋₂₀aryl, C₅₋₂₀arylalkyl, C₁₋₂₀ alkoxy, C₅₋₂₀aryloxyor C₅₋₂₀arylalkoxy;

Optionally, R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄,R₁₅ and R₁₆ are all hydrogen.

Optionally, M is Ga(A¹), such as Ga(OCH₂CH₂OCH₂CH₂OCH₂CH₂OMe); that iswhere R^(q) is CH₂CH₂OCH₂CH₂OCH₂CH₂OMe. For the avoidance of doubt,ethers such as CH₂CH₂OCH₂CH₂OCH₂CH₂OMe fall within definition of alkylgroups as specified hereinbelow. Gallium compounds are preferred sincethey have excellent lightfastness, strong, absorption in the near-IRregion, and are virtually invisible to the human eye when printed on apage.

Optionally, step (iii) comprises heating the benzisoindolenine in thepresence of a metal compound, such as AlCl₃ or GaCl₃ corresponding metalalkoxide. The reaction may be performed in the absence of or in thepresence of a suitable solvent, such as toluene, nitrobenzene etc. Whena metal alkoxide is used, the reaction may be catalyzed with a suitablebase, such as sodium methoxide. Alcohols, such as triethylene glycolmonomethyl ether or glycol may also be present to assist withnaphthalocyanine formation. These alcohols may end up as the axialligand of the naphthalocyanine or they may be cleaved from the metalunder the reaction conditions. The skilled person will readily be ableto optimize the conditions for naphthalocyanine formation from thebenzisoindolenine.

Optionally, the method further comprises the step of suffocating saidnaphthalocyanine. Sulfonate groups are useful for solubilizing thenaphthalocyanines in ink formulations, as described in our earlier U.S.Pat. Nos. 7,148,345 and 7,122,076.

In a second aspect, there is provided a method of effecting a one-potconversion of a tetrahydronaphthalic anhydride to a benzisoindoleninesalt, said method comprising heating said tetrahydronaphthalic anhydridewith a reagent mixture comprising ammonium nitrate.

This transformation advantageously obviates a separate dehydrogenationstep to form the naphthalene ring system. The ammonium nitrate performsthe dual functions of oxidation (dehydrogenation) and isoindolenineformation.

The isoindolenine salts generated according to the second aspect may beused in the synthesis of naphthalocyanines. Hence, this key reactionprovides a significant improvement in routes to naphthalocyanines.

In general, optional features of this second aspect mirror the optionalfeatures described above in respect of the first aspect.

In a third aspect, there is provided a method of preparing a sultine offormula (V) from a dihalogeno compound of formula (IV)

the method comprising reacting the dihalogeno compound (IV) with ahydroxymethanesulfinate salt in a DMSO solvent so as to prepare thesultine (V);wherein:R₁, R₂, R₃ and R₄ are each independently selected from hydrogen,hydroxyl, C₁₋₂₀alkyl, C₁₋₂₀alkoxy, amino, C₁₋₂₀alkylamino,di(C₁₋₂₀alkyl)amino, halogen, cyano, thiol, C₁₋₂₀alkylthio, nitro, C₁₋₂₀alkylcarboxy, C₁₋₂₀alkylcarbonyl, C₁₋₂₀alkoxycarbonyl,C₁₋₂₀alkylcarbonyloxy, C₁₋₂₀alkylcarbonylamino, C₅₋₂₀aryl,C₅₋₂₀arylalkyl, C₅₋₂₀aryloxy, C₅₋₂₀arylalkoxy, C₅₋₂₀heteroaryl,C₅₋₂₀heteroaryloxy, C₅₋₂₀ heteroarylalkoxy or C₅₋₂₀heteroarylalkyl; andX is Cl, Br or I.

The method according to the third aspect surprisingly minimizespolymeric by-products and improves yields, when compared to literaturemethods for this reaction employing DMF as the solvent. These advantagesare amplified when the reaction is performed on a large scale (e.g. atleast 0.3 molar, at least 0.4 molar or at least 0.5 molar scale).

Optionally, NaI is used to catalyze the coupling reactions when X is Clor Br.

Optionally, a metal carbonate base (e.g. Na₂CO₃, K₂CO₃, Cs₂CO₃ etc) ispresent.

Optionally, the hydroxymethanesulfinate salt is sodiumhydroxymethanesulfinate Rongalite™).

Optionally, R₁, R₂, R₃ and R₄ are all hydrogen.

Optionally, the method comprises the further step of reacting thesultine (V) with an olefin at elevated temperature (e.g., about 80° C.)to generate a Diels-Alder adduct.

Optionally, the olefin is maleic anhydride and said Diels-Alder adductis a tetrahydronaphthalic anhydride.

Optionally, the tetrahydronaphthalic anhydride is used as a precursorfor naphthalocyanine synthesis, as described herein.

Optionally, the naphthalocyanine synthesis proceeds via conversion oftetrahydronaphthalic anhydride to benzisoindolenine, as describedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in detail with reference to thefollowing drawings, in which:

FIG. 1 is a ¹H NMR spectrum of the crude sultine 10 in d₆-DMSO;

FIG. 2 is a ¹H NMR spectrum of the anhydride 8 in d₆-DMSO;

FIG. 3 is a ¹H NMR spectrum of the crude benzisoindolenine salt 12 ind₆-DMSO;

FIG. 4 is an expansion of the aromatic region of the ¹H NMR spectrumshown in FIG. 3;

FIG. 5 is a ¹H NMR spectrum of the benzisoindolenine 7 in d₆-DMSO.

FIG. 6 is an expansion of the aromatic region of the ¹H NMR spectrumshown in FIG. 5; and

FIG. 7 is a UV-VIS spectrum of naphthalocyanatogalliummethoxytriethyleneoxide in NMP.

DETAILED DESCRIPTION

As an alternative to dicarbonitriles, the general class ofphthalocyanines is known to be prepared from isoindolenines. In U.S.Pat. No. 7,148,345, we proposed the benzisoindolenine 5 as a possibleprecursor to naphthalocyanines.

However, efficient syntheses of the benzisoindolenine 5 were unknown inthe literature, and it was hitherto understood that dicarbonitriles,such as naphthalene-2,3-dicarbonitrile 2, were the only viable route tonaphthalocyanines.

Nevertheless, with the potentially prohibitive cost ofnaphthalene-2,3-dicarbonitrile 2, the present inventors sought toexplore a new route to the benzisoindolenine 5, as outlined in Scheme 2.

Tetrahydronaphthalic anhydride 6 was an attractive starting point,because this is a known Diels-Alder adduct which may be synthesized viathe route shown in Scheme 3.

Referring to Scheme 2, it was hoped that the conversion of naphthalicanhydride 7 to the benzisoindolenine 5 would proceed analogously to theknown conversion of phthalic anhydride to the isoindolenine 8, asdescribed in WO98/31667.

However, a number of problems remained with the route outlined in Scheme2. Firstly, the dehydrogenation of tetrahydronaphthalic anhydride 6typically requires high temperature catalysis. Under these conditions,tetrahydronaphthalic anhydride 6 readily sublimes resulting in very pooryields. Secondly, the preparation of tetrahydronaphthalic anhydride 6 ona large scale was not known. Whilst a number of small-scale routes tothis compound were known in the literature, these generally sufferedeither from poor yields or scalability problems.

The use of sultines as diene precursors is well known and1,4-dihydro-2,3-benzoxathiin-3-oxide 10 has been used in a synthesis of6 on a small scale (Hoey, M. D.; Dittmer, D. A. J. Org. Chem. 1991, 56,1947-1948). As shown in Scheme 4, this route commences with therelatively inexpensive dichloro-o-xylene 11, but the feasibility ofscaling up this reaction sequence is limited by the formation ofundesirable polymeric by-products in the sultine-forming step. Theformation of these by-products makes reproducible production of 6 inhigh purity and high yield difficult.

Nevertheless, the route outlined in Scheme 4 is potentially attractivefrom a cost standpoint, since dichloro-o-xylene 11 and maleic anhydrideare both inexpensive materials.

Whilst the reaction sequence shown in Schemes 4 and 2 presentsignificant synthetic challenges, the present inventors havesurprisingly found that, using modified reaction conditions, thebenzisoindolenine 5 can be generated on a large scale and in high yield.Hence, the present invention enables the production of naphthalocyaninesfrom inexpensive starting materials, and represents a significant costimprovement over known syntheses, which start fromnaphthalene-2,3-dicarbonitrile 2.

Referring to Scheme 5, there is shown a route to the benzisoindolenine5, which incorporates two synthetic improvements in accordance with thepresent invention.

Unexpectedly, it was found that by using DMSO as the reaction solvent inthe conversion of 11 into 10, the reaction rate and selectivity for theformation of sultine 10 increases significantly. This is in contrast toknown conditions (Hoey, M. D.; Dittmer, D. A. J. Org. Chem. 1991, 56,1947-1948) employing DMF as the solvent, where the formation ofundesirable polymeric side-products is a major problem, especially on alarge scale. Accordingly, the present invention provides a significantimprovement in the synthesis of tetrahydronaphthalic anhydride 6.

The present invention also provides a significant improvement in theconversion of tetrahydronaphthalic anhydride 6 to the benzisoindolenine5. Surprisingly, it was found that the ammonium nitrate used for thisstep readily effects oxidation of the saturated ring system as well asconverting the anhydride to the isoindolenine. Conversion to atetrahydroisoindolenine was expected to proceed smoothly, in accordancewith the isoindolenine similar systems described in WO98/31667. However,concomitant dehydrogenation under these reaction conditionsadvantageously provided a direct one-pot route from thetetrahydronaphthalic anhydride 6 to the benzisoindolenine salt 12. Thisavoids problematic and low-yielding dehydrogenation of thetetrahydronaphthalic anhydride 6 in a separate step. Subsequenttreatment of the salt 12 with a suitable base, such as sodium methoxide,liberates the benzisoindolenine 5. As a result of these improvements,the entire reaction sequence from 11 to 5 is very conveniently carriedout, and employs inexpensive starting materials and reagents (Scheme 5).

The benzisoindolenine 5 may be converted into any requirednaphthalocyanine using known conditions. For example, the preparation ofa gallium naphthalocyanine from benzisoindolenine 5 is exemplifiedherein. Subsequent manipulation of the naphthalocyanine macrocycle mayalso be performed in accordance with known protocols. For example,sulfonation may be performed using oleum, as described in U.S. Pat. Nos.7,148,345 and 7,122,076.

Hitherto, the use of tetrahydronaphthalic anhydride 6 as a buildingblock for naphthalocyanine synthesis had not previously been reported.However, it has now been shown that tetrahydronaphthalic anhydride 6 isa viable intermediate in the synthesis of these important compounds.Moreover, it is understood by the present inventors that the route shownin Scheme 5 represents the most cost-effective synthesis ofbenzisoindolenines 5.

The term “aryl” is used herein to refer to an aromatic group, such asphenyl, naphthyl or triptycenyl. C₆₋₁₂aryl, for example, refers to anaromatic group having from 6 to 12 carbon atoms, excluding anysubstituents. The term “arylene”, of course, refers to divalent groupscorresponding to the monovalent aryl groups described above. Anyreference to aryl implicitly includes arylene, where appropriate.

The term “heteroaryl” refers to an aryl group, where 1, 2, 3 or 4 carbonatoms are replaced by a heteroatom selected from N, O or S. Examples ofheteroaryl (or heteroaromatic) groups include pyridyl, benzimidazolyl,indazolyl, quinolinyl, isoquinolinyl, indolinyl, isoindolinyl, indolyl,isoindolyl, furanyl, thiophenyl, pyrrolyl, thiazolyl, imidazolyl,oxazolyl, isoxazolyl, pyrazolyl, isoxazolonyl, piperazinyl, pyrimidinyl,piperidinyl, morpholinyl, pyrrolidinyl, isothiazolyl, triazolyl,oxadiazolyl, thiadiazolyl, pyridyl, pyrimidinyl, benzopyrimidinyl,benzotriazole, quinoxalinyl, pyridazyl, coumarinyl etc. The term“heteroarylene”, of course, refers to divalent groups corresponding tothe monovalent heteroaryl groups described above. Any reference toheteroaryl implicitly includes heteroarylene, where appropriate.

Unless specifically stated otherwise, aryl and heteroaryl groups may beoptionally substituted with 1, 2, 3, 4 or 5 of the substituentsdescribed below.

Where reference is made to optionally substituted groups (e.g. inconnection with aryl groups or heteroaryl groups), the optionalsubstituent(s) are independently selected from C₁₋₈alkyl, C₁₋₈alkoxy,—(OCH₂CH₂)_(d)OR^(d) (wherein d is an integer from 2 to 5000 and R^(d)is H, C₁₋₈alkyl or C(O)C₁₋₈alkyl), cyano, halogen, amino, hydroxyl,thiol, —SR^(v), —NR^(N)R^(v), nitro, phenyl, phenoxy, —CO₂R^(v),—C(O)R^(v), —OCOR^(v), —SO₂R^(v), —OSO₂R^(v), —SO₂OR^(v), —NHC(O)R^(v),—CONR^(N)R^(v), —CONR^(N)R^(v), —SO₂NR^(N)R^(v), wherein R^(N) and R^(v)are independently selected from hydrogen, C₁₋₂₀alkyl, phenyl orphenyl-C₁₋₈alkyl (e.g. benzyl). Where, for example, a group containsmore than one substituent, different substituents can have differentR^(N) or R^(v) groups.

The term “alkyl” is used herein to refer to alkyl groups in bothstraight and branched forms. Unless stated otherwise, the alkyl groupmay be interrupted with 1, 2, 3 or 4 heteroatoms selected from O, NH orS. Unless stated otherwise, the alkyl group may also be interrupted with1, 2 or 3 double and/or triple bonds. However, the term “alkyl” usuallyrefers to alkyl groups having double or triple bond interruptions. Where“alkenyl” groups are specifically mentioned, this is not intended to beconstrued as a limitation on the definition of “alkyl” above.

Where reference is made to, for example, C₁₋₂₀alkyl, it is meant thealkyl group may contain any number of carbon atoms between 1 and 20.Unless specifically stated otherwise, any reference to “alkyl” meansC₁₋₂₀alkyl, preferably C₁₋₁₂alkyl or C₁₋₆alkyl.

The term “alkyl” also includes cycloalkyl groups. As used herein, theterm “cycloalkyl” includes cycloalkyl, polycycloalkyl, and cycloalkenylgroups, as well as combinations of these with linear alkyl groups, suchas cycloalkylalkyl groups. The cycloalkyl group may be interrupted with1, 2 or 3 heteroatoms selected from O, N or S. However, the term“cycloalkyl” usually refers to cycloalkyl groups having no heteroatominterruptions. Examples of cycloalkyl groups include cyclopentyl,cyclohexyl, cyclohexenyl, cyclohexylmethyl and adamantyl groups.

The term “arylalkyl” refers to groups such as benzyl, phenylethyl andnaphthylmethyl.

The term “halogen” or “halo” is used herein to refer to any of fluorine,chlorine, bromine and iodine. Usually, however halogen refers tochlorine or fluorine substituents.

Where reference is made herein to “a naphthalocyanine”, “abenzisoindolenine”, “a tetrahydronaphthalic anhydride” etc, this isunderstood to be a reference to the general class of compounds embodiedby these generic names, and is not intended to refer to any one specificcompound. References to specific compounds are accompanied with areference numeral.

Chiral compounds described herein have not been givenstereo-descriptors. However, when compounds may exist in stereoisomericforms, then all possible stereoisomers and mixtures thereof are included(e.g. enantiomers, diastereomers and all combinations including racemicmixtures etc.).

Likewise, when compounds may exist in a number of regioisomeric ortautomeric forms, then all possible regioisomers, tautomers and mixturesthereof are included.

For the avoidance of doubt, the term “a” (or “an”), in phrases such as“comprising a”, means “at least one” and not “one and only one”. Wherethe term “at least one” is specifically used, this should not beconstrued as having a limitation on the definition of “a”.

Throughout the specification, the term “comprising”, or variations suchas “comprise” or “comprises”, should be construed as including a statedelement, integer or step, but not excluding any other element, integeror step.

The invention will now be described with reference to the followingdrawings and examples. However, it will of course be appreciated thatthis invention may be embodied in may other forms without departing fromthe scope of the invention, as defined in the accompanying claims.

EXAMPLE 1 1,4-dihydro-2,3-benzoxathiin-3-oxide 10

Sodium hydroxymethanesulfinate (Rongalite™) (180 g; 1.17 mol) wassuspended in DMSO (400 mL) and left to stir for 10 min. beforedichloro-o-xylene (102.5 g; 0.59 mol), potassium carbonate (121.4 g;0.88 mol) and sodium iodide (1.1 g; 7 mmol) were added consecutively.More DMSO (112 mL) was used to rinse residual materials into thereaction mixture before the whole was allowed to stir at roomtemperature. The initial endothermic reaction became mildly exothermicafter around 1 h causing the internal temperature to rise to ca. 32-33°C. The reaction as followed by TLC (ethyl acetate/hexane, 50:50) andfound to be complete after 3 h. The reaction mixture was diluted withmethanol/ethyl acetate (20:80; 400 mL) and the solids were filtered off,and washed with more methanol/ethyl acetate (20:80; 100 mL, 2×50 mL).The filtrate was transferred to a separating funnel and brine (1 L) wasadded. This caused more sodium chloride from the product mixture toprecipitate out. The addition of water (200 mL) redissolved the sodiumchloride. The mixture was shaken and the organic layer was separated andthen the aqueous layer was extracted further with methanol/ethyl acetate(20:80; 200 mL), 150 mL, 250 mL). The combined extracts were dried(Na₂SO₄) and rotary evaporated (bath 37-38° C.). More solvent wasremoved under high vacuum to give the sultine 10 as a pale orange liquid(126 g) that was found by ¹H NMR spectroscopy to be relatively free ofby-product but containing residual DMSO and ethyl acetate (FIG. 1).

EXAMPLE 2 Tetrahydronaphthalic Anhydride 6

The crude sultine from about (126 g) was diluted in trifluorotoluene(100 mL) and then added to a preheated (bath 80° C.) suspension ofmaleic anhydride (86 g; 0.88 mol) in trifluorotoluene (450 mL). Theresidual sultine was washed with more trifluorotoluene into the reactionmixture and then the final volume was made up to 970 mL. The reactionmixture was heated at 80° C. for 15 h, more maleic anhydride (287 g;0.29 mol) was added and then heating was continued for a further 8 huntil TLC showed that the sultine had been consumed. While still at 80°C., the solvent was removed by evaporation with a water aspirator andthen the residual solvent was removed under high vacuum. The moist solidwas triturated with methanol (200 mL) and filtered off, washing withmore methanol (3×100 mL). The tetrahydronaphthalic anhydride 6 wasobtained as a fine white crystalline solid (75.4 g; 64% from 10) afterdrying under high vacuum at 60-70° C. for 4 h.

EXAMPLE 3

The sultine was prepared from dichloro-o-xylene (31.9 g; 0.182 mol), asdescribed in Example 2, and then reacted with maleic anhydride (26.8 g;0.273 mol) in toluene (300 mL total volume) as described above. Thisafforded the tetrahydronaphthalic anhydride 6 as a white crystallinesolid (23.5 g; 64%).

EXAMPLE 4 1-amino-3-iminobenz[f]isoindolenine nitrate salt 12

Urea (467 g; 7.78 mol) was added to a mechanically stirred mixture ofammonium sulfate (38.6 g; 0.29 mol), ammonium molybdate (1.8 g) andnitrobenzene (75 mL). The whole was heated with a heating mantle to ca.130° C. (internal temperature) for 1 h causing the urea to melt. At thispoint the anhydride 6 (98.4 g; 0.49 mol) was added all at once as asolid. After 15 min ammonium nitrate (126.4 g; 1.58 mol) was added withstirring (internal temperature 140° C.) accompanied by substantial gasevolution. The reaction temperature was increased to 170-175° C. over 45min and held there for 2 h 20 min. The viscous brown mixture was allowedto cool to ca. 100° C. and then methanol (400 mL) was slowly introducedwhile stirring. The resulting suspension was poured on a sintered glassfunnel, using more methanol (100 mL) to rinse out the reaction flask.After removing most of the methanol by gravity filtration, the brownsolid was sucked dry and then washed with more methanol (3×220 mL, 50mL), air-dried overnight and dried under high vacuum in a warm waterbath for 1.5 h. The benzisoindolenine salt 12 was obtained as a finebrown powder (154.6 g) and was found by NMR analysis to contain urea(5.43 ppm) and other salts (6.80 ppm). This material was used directlyin the next step without further purification.

EXAMPLE 5 1-amino-3-iminobenz[f]isoindolenine 7

The crude nitrate salt 12 (154.56 g) was suspended in acetone (400 mL)with cooling in an ice/water bath to 0° C. Sodium methoxide (25% inmethanol; 284 ml; 1.3 mol) was added slowly drop wise via a droppingfunnel at such a rate as to maintain an internal temperature of 0-5° C.Upon completion of the addition, the reaction mixture was poured intocold water (2×2 L) in two 2 L conical flasks. The mixtures were thenfiltered on sintered glass funnels and the solids were washed thoroughlywith water (250 mL; 200 mL for each funnel). The fine brown solids wereair-dried over 2 days and then further dried under high vacuum to givethe benzisoindolenine 5 as a fine brown powder (69.1 g; 73%).

EXAMPLE 6 Naphthalocyanatogallium Methoxytriethyleneoxide

Gallium chloride (15.7 g; 0.089 mol) was dissolved in anhydrous toluene(230 mL) in a 3-neck flask (1 L) equipped with a mechanical stirrer,heating mantle, thermometer, and distillation outlet. The resultingsolution was cooled in an ice/water bath to 10° C. and then sodiummethoxide in methanol (25%; 63 mL) was added slowly with stirring suchthat the internal temperature was maintained below 25° C. therebyaffording a white precipitate. The mixture was then treated withtriethylene glycol monomethyl ether (TEGMME; 190 mL) and then the wholewas heated to distill off all the methanol and toluene (3 h). Themixture was then cooled to 90-100° C. (internal temperature) by removingthe heating mantle and then the benzisoindolenine 5 from the previousstep (69.0 g; 0.35 mol) was added all at once as a solid with the lasttraces being washed into the reaction vessel with diethyl ether (30 mL).The reaction mixture was then placed in the preheated heating mantlesuch that an internal temperature of 170° C. was established after 20min. Stirring was then continued at 175-180° C. for a further 3 h duringwhich time a dark green/brown colour appeared and the evolution ofammonia took place. The reaction mixture was allowed to cool to ca. 100°C. before diluting with DMF (100 mL) and filtering through a sinteredglass funnel under gravity overnight. The moist filter cake was suckeddry and washed consecutively with DMF (80 mL), acetone (2×100 mL), water(2×100 mL), DMF (50 mL), acetone (2×50 mL; 100 mL) and diethyl ether(100 mL) with suction. After brief air drying, the product was driedunder high vacuum at 60-70° Co constant weight. Naphthalocyanatogalliummethoxytriethyleneoxide was obtained as a microcrystalline darkblue/green solid (60.7 g; 76%); λ_(max) (NMP) 771 nm (FIG. 7).

1. A method of preparing a naphthalocyanine comprising the steps of: (i)providing a tetrahydronaphthalic anhydride of formula (I):

(ii) converting said tetrahydronaphthalic anhydride to abenzisoindolenine of formula (II):

(iii) macrocyclizing said benzisoindolenine to form a naphthalocyanineof formula (III):

wherein: R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄,R₁₅ and R₁₆ are each independently selected from hydrogen, hydroxyl,C₁₋₂₀ alkyl, C₁₋₂₀ alkoxy, amino, C₁₋₂₀ alkylamino, di(C₁₋₂₀alkyl)amino, halogen, cyano, thiol, C₁₋₂₀ alkylthio, nitro, C₁₋₂₀alkylcarboxy, C₁₋₂₀ alkylcarbonyl, C₁₋₂₀ alkoxycarbonyl, C₁₋₂₀alkylcarbonyloxy, C₁₋₂₀ alkylcarbonylamino, C₅₋₂₀ aryl, C₅₋₂₀ arylalkyl,C₅₋₂₀ aryloxy, C₅₋₂₀ arylalkoxy, C₅₋₂₀ heteroaryl, C₅₋₂₀ heteroaryloxy,C₅₋₂₀ heteroarylalkoxy or C₅₋₂₀ heteroarylalkyl; M is absent or selectedfrom Si(A¹)(A²), Ge(A¹)(A²), Ga(A¹), Mg, Al(A¹), TiO, Ti(A¹)(A²), ZrO,Zr(A¹)(A²), VO, V(A¹)(A²), Mn, Mn(A¹), Fe, Fe(A¹), Co, Ni, Cu, Zn, Sn,Sn(A¹)(A²), Pb, Pb(A¹)(A²), Pd and Pt; A¹ and A² are axial ligands,which may be the same or different, and are selected from OH, halogen orOR^(q); R^(q) is selected from C₁₋₁₆ alkyl, C₅₋₂₀ aryl, C₅₋₂₀ arylalkyl,C₁₋₂₀ alkylcarbonyl, C₁₋₂₀ alkoxycarbonyl or Si(R^(x))(R^(y))(R^(z));and R^(x), R^(y) and R^(z) may be the same or different and are selectedfrom C₁₋₂₀ alkyl, C₅₋₂₀ aryl, C₅₋₂₀ arylalkyl, C₁₋₂₀ alkoxy, C₅₋₂₀aryloxy or C₅₋₂₀ arylalkoxy.
 2. The method of claim 1, wherein R₁, R₂,R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅ and R₁₆ are allhydrogen.
 3. The method of claim 1, wherein step (ii) comprises aone-pot conversion from the tetrahydronaphthalic anhydride of formula(I) to a salt of the benzisoindolenine of formula (II).
 4. The method ofclaim 3, wherein said salt is a nitrate salt.
 5. The method of claim 3,wherein said one-pot conversion is effected by heating with a reagentmixture comprising ammonium nitrate.
 6. The method of claim 5, whereinsaid reagent mixture comprises at least 2 equivalents of ammoniumnitrate with respect to said tetrahydronaphthalic anhydride of formula(I).
 7. The method of claim 5, wherein said reagent mixture comprisesurea.
 8. The method of claim 5, wherein said reagent mixture comprisesat least one further ammonium salt.
 9. The method of claim 8, whereinsaid at least one further ammonium salt is selected from the groupconsisting of: ammonium sulfate and ammonium benzenesulfonate.
 10. Themethod of claim 5, wherein said reagent mixture comprises ammoniummolybdate.
 11. The method of claim 5, wherein said heating is within atemperature range of 150 to 200° C.
 12. The method of claim 11, whereinsaid heating is in the presence of a solvent selected from the groupconsisting of: nitrobenzene, diphenyl, diphenyl ether, mesitylene,anisole, phenetole, dichlorobenzene, trichlorobenzene and mixturesthereof.
 13. The method of claim 3, wherein the benzisoindolenine offormula (II) is liberated from the benzisoindolenine salt using sodiummethoxide.
 14. The method of claim 1, wherein M is Ga(A¹).
 15. Themethod of claim 1, wherein step (iii) comprises heating saidbenzisoindolenine of formula (II) in the presence of GaCl₃.